Justificación

“This method [transgenic expression in milk] permits flexible scale-up of protein manufacturing to meet increasing production needs throughout the product

development process. Scale-up is as simple as breeding more transgenic animals.”

Genzyme Transgenics website, 30th September 2001¹⁹³.

“Phenotype and genotype cannot be reliably defined in transgenic animals until successive generations of offspring obtained from outbreeding with nontransgenic animals are analyzed.”

Butler et al, 1997⁶².

The potential risks to human health from pharmaceutical production in GM animals give cause for concern. There are two main areas of risk - cross species disease transmission and that altered or novel proteins from descendants of GM founder animals may surface after the initial regulatory period has passed.

There is a risk of cross species pathogen transmission or viral contamination with any animal product⁹³. A small possibility of catching a new disease may be a justifiable risk for someone already suffering from a life threatening illness. However, new pathogens crossing the species barrier could enter the population at large because of the risk of onward transmission. This is especially worrying in the light of recent experiences with BSE.

Any new pharmaceutical product is required to pass extensive safety tests before being made available for public use; and release may still result in unexpected, and sometimes serious, effects as the drug is given to a wide variety of people in greatly different circumstances. Subtle changes in a protein’s structure can significantly alter it’s effects. The assumption that

descendants of a transgenic founder will produce identical proteins in their milk may not be justified.

The transgenic process is random, frequently resulting in integration of multiple copies of the transgene and damage to the animal’s own genes^59,69.All of these effects can be masked by heterozygosity so that effects on both the transgenic product and the animal may not surface for generations. It has to be asked at what point the regulatory process regarding transgenic

pharmaceuticals will be completed – is a product line regarded as stable after three generations?

Seven generations? Will the products resulting from the ‘simple scale-up’ referred to in the Genzyme Transgenics website be subject to the same rigorous scrutiny as the initial product?

Much is also made of the ability of transgenic animals to correctly process human proteins. It is likely that proteins produced in transgenic animals – and the other production systems – are each different⁹³. In one study, glycosolation and functional properties were compared between native (human) superoxide dismutase (SOD), SOD produced in Chinese hamster ovary cells, and transgenic SOD produced in rabbit milk. (Superoxide dismutase is a major enzyme in plasma, lymph and synovial fluid.) Functional properties were similar although glycosolation was slightly different in all three cases⁹². The closest match is likely to be human cells in culture.

6.5 Conclusion

Pharmaceutical production in transgenic animals is one method of supplying drugs, which may in some instances be the easiest means of meeting bulk requirements. However, there are

alternative production systems that could meet requirements – bacterial and mammalian cell cultures, transgenic plants, and transgenic plant cell cultures. All of these systems have

drawbacks as well as advantages. At present, by far the most important deciding factor on which system is developed is potential profit.

There is a need for a systematic appraisal of the different systems which takes into account the technical, social and ethical aspects of how society is to meet the need for drugs. It is likely that the first choice would be mammalian cell culture, which may also have the potential to offer the highest quality product¹⁸⁷.

7. AGRICULTURE

“To date attempts [to engineer livestock for use in agriculture] have failed to result in the production of genetically superior livestock (sheep and pigs) due to a variety of undesirable side effects in these animals, although the transgenic animals have been more feed efficient and leaner.”

Pinkert and Murray, 1999¹⁵³.

Most of the transgenic animals being developed are either for medical purposes (research or organ production) or for the production of high value pharmaceuticals. However, several research groups around the world, including major government and academic laboratories (e.g. CSIRO in Australia and USDA in USA), are attempting to develop transgenic cows, sheep and pigs with increased agricultural productivity. There are also attempts to engineer increased disease resistance. Table 7 lists the transgenic animals which have been produced and their intended agricultural use. Twenty-one of the thirty-four genetic modifications listed are aimed at increased productivity.

There are two fundamental questions regarding transgenic growth enhancement – firstly, and most importantly, is it necessary? - Does the world need a marginal decrease in the time taken for pigs to reach slaughter weight or a 10% increase in wool production or in the protein content of milk? Secondly, are transgenic attempts to enhance productivity likely to be successful without severely compromising the welfare of the animals involved?

Feeding an increasing world population is often put forward as a reason to develop transgenic agriculture ^e.g.6,7. Global food production will need to rise as population increases but global output is not the key determinant of whether people are adequately nourished. 790 million people in developing countries and 34 million people in developed countries are malnourished now, despite the fact that gross world food production is sufficient to feed every person on the planet

adequately¹⁹⁴. The reasons for malnutrition are chiefly poverty, in that access to food is

determined by income, and the disparity in regional agricultural productivity¹⁹⁵ – neither of which will be affected by the gene constructs which are currently being inserted into animals.

Growth enhancement work is aimed at breeds that are already very high producers, dependent on intensive farming methods including high protein diets. Any meaningful rise in agricultural productivity would need to be in areas of the world which are currently experiencing low food availability¹⁹⁵. However, these are generally not areas in which intensive livestock systems are used. Nor would a switch to intensive methods increase food availability because of the relationship between meat production and protein in such systems. The production of one kilogram of beef in the developed world is estimated to require five kilograms of plant protein, most of which could be eaten directly by humans¹⁹⁶. Increasing intensive meat production is not a recipe for improving food availability. The same argument applies to milk production, with the further dimension that milk is currently produced on a quota system in most OECD countries to restrict supplies¹⁹⁷. It is hard to see the logic in increasing either milk production per se or the protein content of milk in areas of the world where there is already an oversupply. Increases in transgenic breeds’ productivity are likely to be profitable for the intensive livestock industry but there is no reason to think they would improve world food security.

Is it likely that productivity can be directly enhanced by transgenic methods without detrimental effects on the animals? With the exception of alterations to milk composition, the traits to be altered are complex – growth or metabolism of nutrients. Modern agricultural breeds in intensive livestock systems have already been pushed to their limits to increase production - a dairy cow in an intensive system can now produce 6,400 litres of milk per season compared with 2,000 only 70 years ago¹⁹⁸, and a broiler chicken reaches slaughter weight in just 6 weeks, compared to 12 weeks 30 years ago¹². It is unlikely that an introduced gene would be able to increase growth

without compromising the animal. In the words of a keen proponent of the technology:

“Transgenic research for livestock is directed towards improved animal

productivity….To achieve this it is usually necessary to modify some component of the animal’s physiology, thus potentially altering the existing delicate balance of nutrition, endocrinology and metabolism. Since this balance has been established through many generations of selection for superior performance and environmental compatibility, it represents a wide range of optimised gene combinations that are difficult to perturb without causing unexpected deleterious effects on animal phenotype.”

Kevin Ward, CSIRO, 1999¹⁹⁹.